PERSONAL DE APOYO
FANELLI Silvia Laura
congresos y reuniones científicas
Effect of repetitive alcohol administration on the rat liver nuclear or microsomal bioactivation of carbon tetrachloride and on the oxidative stress promotion
CASTRO J.A., DÍAZ GÓMEZ M.I., FANELLI S.L.
Washington D.C., USA
Congreso; Experimental Biology 2004.; 2004
Federation of American Societies for Experimental Biology (FASEB) International Union of Physiological Sciences (IUPS))
Our laboratory reported the presence in rat liver nuclei of an ethanol (ETOH) metabolizing system (NEMS) able to lead to acetaldehyde and to 1-hydroxyethyl free radicals. NEMS and the well known microsomal ethanol metabolizing system (MEOS) are CYP 2E1-dependent and both are inducible by repetitive alcohol drinking. This may enhance the toxic/carcinogenic response of alcohol treated animals when exposed to other chemicals bioctivated via CYP 2E1 such as CCl4. We found that nuclei and microsomes from EtOH pretreated rats showed increased covalent binding of their reactive metabolites to proteins but not to lipids. The peroxidability of nuclear or microsomal lipids as determined by hydroperoxide-induced chemiluminiscence was enhanced in the EtOH pretreated rats. The protein sulfhydryl content of nuclear or microsomal proteins was significantly decreased in EtOH pretreated animals. This effect was significantly diminished when the subcellular fractions were incubated with CCl4 both in the presence or absence of NADPH. Nuclear proteins from ethanol pretreated rats exhibited increased protein carbonyl formation when incubated with CCl4 either in the presence or absence of NADPH. Results suggest that repetitive liver exposure to ethanol increased not only the NEMS or MEOS activities but also the protein carbonyl content, decreased the protein SH content of nuclear proteins and enhanced the biotransformation of other CYP 2E1 mediated compounds such as CCl4.